Polyelectrolytes have been used extensively in biomaterials as the electrostatic interaction of oppositely charged polymers allow for their self-assembly into various polyelectrolyte complexes.1,2 However, high charge density polyelectrolytes, in particular polycations, sometimes show poor biocompatibility due to protein binding and cytotoxicity. The standard alginate-poly(L-lysine)-alginate (APA) capsule, composed of calcium alginate cores coated with poly(L-lysine) (PLL) and a final alginate layer, for encapsulation and immuno-isolation of mammalian cells as an approach to cell-based therapies for enzyme and hormone deficiency disorders, has shown issues with mechanical stability and biocompatibility.3,4 As the APA capsule is held together solely by electrostatic interactions (Ca-alginate and alginate-PLL), its long-term stability in vivo can be compromised by processes such as exchange of calcium for sodium in the serum.5 Although the high-charge density poly(L-lysine) (PLL) allows for strong electrostatic complexation with alginate, it is desirable to covalently crosslink the polyelectrolyte complex to ensure long-term stability of the capsule shell. In addition, it can be advantageous to hide the PLL on the capsule surface to avoid adverse immune responses including cellular overgrowth triggered by cationic patches and hydrophobic complexes.6,7 
One approach has been to use temporarily reactive polyanions (TRPs) that can a) form a 1:1 charge complex with, e.g., PLL coated onto calcium alginate, b) form permanent covalent crosslinks (amide linkages) by reaction of electrophilic units with amines on the polycation and e) undergo hydrolysis of residual electrophilic units to give an overall anionic charge to the complex.7,8 
While PLL has been shown to be suitable for this process, attempts have been made to reduce the detrimental effects of such high-charge density polycations in biomaterial applications. These include design and synthesis of copolymers combining cationic monomers with neutral, polar9 or anionic10 comonomers, grafting poly(ethylene glycol) chains onto PLL,11,12 and cross-linking alginate-PLL capsules with tosylated poly(vinyl alcohol).13 
Many of these charge-reduced polycations suffer from relatively weak electrostatic binding to the calcium alginate cores. Thus, a polymer with a high cationic charge density, able to form strong polyelectrolyte complexes with alginate, is needed for initial deposition, though a mechanism of cationic charge reduction is desirable for host-compatibility of the final hydrogel.
There has been recent interest in polyelectrolytes able to reduce or switch the charge on a polymer chain, a process that typically occurs by hydrolysis. These polymers, often called “charge-shifting”, “charge-reversing” or “charge-conversion” polymers, are of particular interest for biomaterial applications where the high initial charge allows them to be self-assembled as polyelectrolyte complexes and then disassembled once the charge has reversed or shifted.14-16 It was first reported by McCool and Senogles that poly(N,N-dimethylaminoethyl acrylate), p(DMAEA), undergoes a self-catalyzed hydrolysis in water to form acrylic acid (AA) units and N,N-dimethylaminoethanol (DMAE) as a by-product.17 More recently, Monteiro et al. explored the preparation and hydrolysis (charge-shifting) of various DMAEA-containing polymers with potential applications as DNA or siRNA delivery devices.18-20 
It would be desirable to develop novel immune-compatible polymer systems useful for cell encapsulation.